Method and apparatus for using adaptive optics in a scanning laser ophthalmoscope

ABSTRACT

A scanning laser ophthalmoscope incorporates adaptive optics to compensate for wavefront aberrations in the eye. Light from a light source is scanned onto the retina. Light reflected from the retina is detected for imaging and is also used for wavefront sensing. The sensed wavefront aberrations are used to control an adaptive optic device, such as a deformable mirror, disposed in the path of the light from the source in order to compensate for the aberrations.

REFERENCE TO RELATED APPLICATION

The present application claims the benefit of U.S. ProvisionalApplication No. 60/316,173, filed Aug. 30, 2001, whose disclosure ishereby incorporated by reference in its entirety into the presentdisclosure.

STATEMENT OF GOVERNMENT INTEREST

The present invention was developed under NIH Grant No. R1 EY 13299-01and NSF Grant No. AST 9876783. The government has certain rights in theinvention.

FIELD OF THE INVENTION

The present invention is directed to scanning laser ophthalmoscopes(SLO) and methods of using them, and more particularly to suchophthalmoscopes and methods of using them which involve the use ofadaptive optics (AO) to compensate for wavefront aberrations in the eyeunder examination.

DESCRIPTION OF RELATED ART

The development of ocular imaging has progressed since the firstscanning laser ophthalmoscope (SLO) was disclosed in U.S. Pat. No.4,213,678. The first patent relating to imaging the ocular fundus whilecorrecting for eye aberrations was Bille's patent titled, “Method andApparatus for forming an image of the ocular fundus” (U.S. Pat. No.4,579,430). A scanning laser ophthalmoscope for high lateral-resolutionimaging was developed which was capable of imaging a living human eyebut did not use adaptive optics (AO) and had limited resolution at themicroscopic level.

The first published report of using AO in a SLO was by Dreher et al,“Active optical depth resolution improvement of the laser tomographicscanner,” App. Opt. 28, 804-808 (1989), to improve the axial resolutionof their instrument. The authors of that article did not use a wavefrontsensor to measure the aberrations of the eye, and their wavefrontcorrector was used only to compensate for the astigmatism of the eye.Similarly, the axial resolution of a SLO has been improved by using arigid contact lens to eliminate the aberrations of the cornea, andmodest improvements in a fundus image has been obtained with a funduscamera equipped with a membrane deformable mirror. Liang et al,“Supernormal vision and high-resolution retinal imaging through adaptiveoptics,” J. Opt. Soc. Am. A 14, 2884-2892 (1997), used an ophthalmoscopeequipped with AO to image microscopic structures in the retina, but theydid not apply the technology to a SLO.

In U.S. Pat. No. 6,095,651, a Hartmann-Shack wavefront sensor andwavefront compensation device are used to measure the high-orderaberrations of the eye. A Hartmann-Shack wavefront sensor was also usedby Bille in U.S. Pat. No. 6,155,684 to measure aberrations for wavefrontcompensation as a means to improve vision. A modified Hartmann-Shackwavefront sensor is described by Williams et al. in U.S. Pat. No.6,199,986, wherein a method for real time measurement of the aberrationsof the eye is described.

Therapeutic applications of SLOs with AO include microphotocoagulationand photodynamic therapy. In U.S. Pat. No. 6,186,628, Van de Veldedescribes the use of a scanning laser ophthalmoscope with an adaptiveelement for microphotocoagulation and photodynamic therapy. Thewavefront sensing technique, described in another patent, entitled“Scanning laser ophthalmoscope for retinal microphotocoagulation andmeasurement of wavefront aberrations” (U.S. Pat. No. 5,943,117) employsa SLO to measure the wavefront aberrations of the eye. This technique isnot used widely.

Although there are a number of patents covering SLO's, they do notpropose a method for wavefront sensing whereby the light path isscanned/descanned using the same optics and light source as that usedfor imaging the ocular fundus. Methods that do not use the same opticsfor wavefront sensing and light detection are subject to a commonphenomena called “non-common path errors,” where the aberrations on thepath to the wavefront sensor are different than those reaching the lightdetector for imaging.

By implementing AO to measure and correct high-order aberrations in anareal imaging system, such as a CCD camera or a film camera, the qualityof retinal images will be improved. However, areal imaging techniquesare limited in that they cannot suppress light from layers in front ofor behind the focal plane of the ophthalmoscope. Because of thislimitation, the images may have high resolution, but will suffer fromlow contrast because of scattered light from structures outside of thebest focal plane.

To date, there has been no successful application of AO into a SLO. Theone previous design published by Dreher et al. did not include wavefrontsensing in the measurement. The benefits of AO cannot be realizedwithout wavefront sensing being an integral part of the system. Bille'sabove-cited patent describes a design for a SLO that integrates awavefront sensor into the design, but it does not use the same path asthe light detection path and is therefore subject to the problem ofnon-common path errors.

SUMMARY OF THE INVENTION

It will be apparent from the above that a need exists in the art tointegrate adaptive optics into retinal imaging. It is therefore anobject of the invention to provide a scanning laser ophthalmoscope withadaptive optics.

It is another object of the invention to do so while avoiding non-commonpath errors.

It is a further object of the invention to provide axial sectioning in ascanning laser ophthalmoscope.

To achieve the above and other objects, the present invention isdirected to a system and method whereby AO can be efficiently andeffectively implemented in a scanning laser ophthalmoscope. The presentinvention will be an improvement on instruments used to take microscopicimages of the retina in living human eyes and will have improved opticalsectioning capability over currently available SLO's.

The present invention's implementation of AO is efficient because ituses the same optical path as the SLO. The present invention'simplementation is effective because it is designed to optimize imagequality, both axially and laterally, over the entire field of view ofthe ophthalmoscope.

The SLO is a device used to take images of the retina of a living humaneye. In the SLO, scattered light is measured from a focused spot oflight as it is scanned across the retina in a raster pattern. The imageis built over time, pixel by pixel, as the spot moves across the retina.An aperture conjugate to (in the image plane of) the desired focal planein the retina and prior to the light detector can be used to reducescattered light originating from planes other than the plane of focus.The confocal aperture can be used to do optical slicing, or imaging ofdifferent layers in the human retina.

AO describes a set of techniques to measure and compensate foraberrations, or optical defects, in optical systems. AO, when applied tothe optical system of the eye, can provide substantial improvements inthe sharpness of retinal images that are normally degraded from theaberrations. Implementation of AO requires the use of a wavefrontsensor, which is a device to measure the aberrations of the opticalsystem, and a wavefront corrector, which is a device used to compensatefor the aberrations in an optical system.

In one particular embodiment, the adaptive optics scanning laserophthalmoscope wavefront sensing, wavefront compensation and rasterscanning.

(i) Light delivery: Light delivery can be from a plurality of lasersources of different wavelengths, depending on the application. Light isrelayed through the instrument via mirrors, which do not suffer fromchromatic aberration. Furthermore, unlike lenses, mirrors do not produceback reflections that can enter into the light detection arm.

(ii) Light detection: Light is detected with a detector such as a verysensitive light detector and amplifier; in a preferred embodiment, aphotomultiplier tube is used. Prior to the light detector in thepreferred embodiment is the confocal pinhole, which is placed conjugateto the focal plane of the system. The confocal pinhole is used to limitlight reaching the detector to that originating from the plane of focus.

(iii) Wavefront sensing: Wavefront sensing takes place in the detectionarm of the instrument. The wavefront sensor measures the optical defectsof the eye in the plane of the entrance pupil.

(iv) Wavefront compensation: Wavefront compensation is done withadaptive optics such as a deformable mirror. The shape of the deformablemirror is set to exactly compensate the distortions in the light thatare caused by the aberrations of the eye.

(v) Raster scanning: Raster scanning is used to move the focused spotacross the retina in a raster pattern. The extent of the pattern definesthe area of the retina that is being imaged. Positional outputs from thescanning mirrors, combined with scattered intensity information from thelight detector, are used to reconstruct the retinal image. Setting thesweep angle on the scanning mirrors controls the field size of theimage.

During operation of the embodiment just described, light is beingscanned in a raster pattern across the retina. The input light beam isstationary from light delivery through the deformable mirror and up tothe first scanning mirror. The horizontal scanning mirror adds ahorizontal sweeping motion to the beam. The second scanning mirror addsa vertical sweep to the beam. Both sweeping motions are done in planesthat are optically conjugate to the pupil of the eye so that the beam atthe plane of the pupil is stationary but it still makes a raster patternon the retina. This property is accomplished by using relay opticsbetween each beam-altering element in the system. According to the lawof reversibility of light, the scattered light from the focused spot onthe retina returns along the same path that the light traveled togenerate the spot. In other words, the scattered light follows thescanning beam but in the opposite direction. The scattered light alsogets descanned after passing through the same raster scanning mirrors.By the time the returning light has passed the horizontal scanningmirror, the beam is again stationary. Aberrations in the scattered lightare compensated by the deformable mirror and are bounced off a beamsplitter into the light detection and wavefront sensing path of theAOSLO. Having a stationary beam in the light detection arm allows thescattered light to be focused through a fixed confocal pinhole, whichgives the SLO its optical sectioning capability.

Light is scanned over the retina in a raster pattern while the beamremains stationary in the plane of the pupil. After scattering, theoptics of the SLO descan the beam and image the pupil of the eye ontothe lenslet array of the Hartmann-Shack wavefront sensor, or thecorresponding element of another wavefront sensor, e.g., a scanningwavefront sensor. The pupil is conjugate to the lenslet array, whichmeans that the aberrations are measured in the pupil plane of the eye.The focused spots in the Hartmann-Shack wavefront sensor image are alsostationary because the beam has been descanned. An image of the focusedspot array in the Hartmann-Shack sensor is obtained by taking a timeexposure of the focused spots with a CCD array detector. These spotimages are analyzed to determine the aberrations of the eye beingmeasured. In a typical Hartmann-Shack wavefront measurement, theaberrations are measured for light originating from a stationary focusedspot on the retina. In high-speed ophthalmic Hartmann-Shackapplications, a system that employs a linear scanning spot has beendeveloped. In this implementation, the source of the light on the retinais constantly moving in a raster during the time exposure, and theHartmann-Shack sensor measures the average wavefront aberration over theentire field of the image. The aberration over the image field isexpected to change slightly because aberrations change with off-axisobject position. Nonetheless, these changes are small since it has beendemonstrated that the eye is nearly isoplanatic over a one-degree field.Therefore, the use of a scanning beam as the source does not present adisadvantage to the measurement, but rather it presents several uniqueadvantages, which are listed below:

1) By using the same light source for wavefront sensing and imaging, theoptics are simplified (no additional light source is necessary forwavefront sensing), and no correction has to be made for the chromaticaberration of the eye between the wavefront sensing and imagingwavelengths.

2) Wavefront sensing is always done on the same retinal region as theimages that are taken, since the source of the wavefront measurement isalso the imaging light.

3) Measuring and compensating the average wavefront over the entireimage field will result in a more uniform correction for aberrations,which will result in better image quality over the field.

4) Wavefront measurements are not affected by noise due to laser specklesince the time-averaged image of a moving spot on the retina despecklesthe image. This advantage has already been applied to wavefront sensingbut not to its application for SLO.

5) The wavefront-sensing configuration described here is easilyadaptable to real-time wavefront sensing and compensation. Thisadvantage stems from the fact that the wavefront sensing signal isalways present during imaging since imaging and wavefront sensing usethe same light source.

6) The optical path to the wavefront sensor is the same as to thephotomultiplier, with the exception of three aberration-correctedachromatic lenses (two in the wavefront sensor path and one in thephotomultiplier path). The aberrations that are measured in thewavefront sensor will be the same as the aberrations of the lightreaching the confocal pinhole, which reduces the non-common path errors.

In at least one embodiment, the wavefront compensation is done with adeformable mirror (DM) placed conjugate to the pupil in the stationarypart of the optical path, prior to the raster scanning mirrors. Havingthe DM in this part of the path means that the mirrors that are used tofocus the pupil image onto the DM can be as small as the maximum beamdiameter and do not have to be enlarged to enclose the maximum scanangle. This reduces the size and cost of the instrument and maintainsbetter image quality in the optics of the instrument.

By using AO in a SLO, the lateral resolution of retinal images isexpected to improve by up to three times. This has already beendemonstrated in conventional ophthalmoscopes equipped with AO. The mainadvantage of applying AO in a SLO will be the improvements in axialresolution. The axial resolution may be improved by up to 10 times overconventional SLO's.

Equivalent Technologies: Successful implementation of AO in a SLO doesnot rely on the specific technologies described in this disclosure. Thefollowing two paragraphs describe equivalent AO technologies that can beimplemented with the same advantages.

Any wavefront sensing technology can be employed that is based onobjective measurement and does not rely on coherent light to perform thewavefront measurement. Alternative techniques include but are notlimited to laser ray tracing techniques, Tscherning aberroscopictechniques and crossed-cylinder aberrometer techniques.

Any wavefront compensation technique can be employed that does not relyon the use of coherent light. Alternative methods for wavefront sensinginclude, but are not limited to, liquid crystal spatial lightmodulators, micro-electro-machined (MEMs) membrane mirrors, MEMssegmented mirrors, bimorph deformable mirrors and electrostatic membranedeformable mirrors.

One set of applications involves the direct imaging applications thatwill benefit from high-resolution images. Such applications include theearly diagnosis of retinal disorders like diabetic retinopathy,retinitis pigmentosa, age-related macular degeneration, or glaucoma.Other applications will be to visualize structures in the retina such asthe nerve fibers, cone and rod photoreceptors, single capillaries in theretina and choroid, and retinal pigmented epithelium cells.High-resolution imaging will help retinal surgeons maintain a sharperimage of the retina during retinal surgery.

Another set of applications are those whereby the SLO is used to imagethe retina at 30 frames per second and is used to observe directly theflow of single white blood cells.

Another set of applications are those where stimuli or treatment lasersare projected directly onto the retina as part of the raster scan. Theseapplications include photodynamic therapy, laser microphotocoagulation,microperimetry of the retina, and eye tracking.

The SLO can use a confocal pinhole to suppress light from outside of thefocal plane, which gives the SLO its optical slicing capability. Thisproperty of the SLO can be improved by implementing AO to measure andcorrect the aberrations of the eye. By reducing the aberrations of theeye through AO compensation, both axial and lateral resolution can beimproved.

BRIEF DESCRIPTION OF THE DRAWINGS

A preferred embodiment of the present invention and variations thereofwill be disclosed in detail with reference to the drawings, in which:

FIG. 1 is a schematic diagram of a scanning laser ophthalmoscopeincorporating adaptive optics;

FIG. 2 is a flow chart of operational steps carried out with theophthalmoscope of FIG. 1;

FIG. 3 is a graph of detected wavefront aberrations for multipleiterations of wavefront sensing and compensation;

FIG. 4 is a graph of a horizontal angular position of a scanning line onthe retina;

FIGS. 5A and 5B are schematic diagrams of a time-share beam splitterusable in the ophthalmoscope of FIG. 1;

FIGS. 6A and 6B show images of a retina taken without and withaberration correction, respectively;

FIGS. 7A-7C show images taken of different axial sections of a retina;

FIG. 8 shows a video image sequence in which a blood cell is movingthrough a retinal capillary; and

FIG. 9 shows images of cone cells taken at various locations on a retinaand calculations of their spacing.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A preferred embodiment of the present invention and variations thereofwill now be set forth in detail with reference to the drawings, in whichlike reference numerals refer to like elements or operational stepsthroughout.

FIG. 1 shows a schematic diagram of the scanning laser ophthalmoscopeusing adaptive optics (AOSLO). In FIG. 1, points on the optical pathwhich are conjugate to the pupil of the eye are labeled p, while pointson the path that are conjugate to the retina are labeled r.

As mentioned above, the AOSLO 100 includes a light delivery section 102,a light detection section 104, a wavefront sensing section 106, awavefront compensation section 108 and a raster scanning section 110.All five sections are under the control of a computer 112.

In the light delivery section 102, light from a fiber optic light source114 is expanded by a beam expander 116 and collimated by a collimatinglens 118. The collimated light is made incident on an artificial pupil120 to produce a smaller beam of light, which is injected into thecommon optical path O of the AOSLO 100 by a 5% reflecting beam splitter122.

Once in the optical path O, the light is reflected by spherical mirrors124 and 126 to the wavefront compensation section 108. Mirrors are usedboth to fold the optical path, thereby making the system more compact,and to avoid the problems of chromatic aberration and back reflectionthat affect lenses. The wavefront compensation section 108 includes adeformable mirror 128. As known in the art, the deformable mirror 128includes a deformable mirror surface 130 deformed by multiple actuators(e.g., piezoelectric actuators) 132. An example of a deformable mirroris the 37-channel deformable mirror produced by Xinetics, Andover, Mass.The deformable mirror 128 is placed in the common optical path Oconjugate to the entrance pupil of the eye E. Under the control of thecomputer 112, the actuators 132 deform the mirror surface 130 tocompensate for wavefront aberrations in a manner that will be describedin detail below.

Light reflected from the mirror surface 132 is reflected to a sphericalmirror 134 and thence to the raster scanning section 110. In the rasterscanning section 110, the light is reflected via a spherical mirror 136to a horizontal scanning mirror 138, which is implemented as a resonantscanner under control of the computer 112. The light horizontallyscanned by the horizontal scanning mirror 138 is reflected via twospherical mirrors 140 and 142 to a vertical scanning mirror 144, whichis implemented as a galvanometric scanner under control of the computer112. A resonant scanner-galvanometric scanner combination produced byElectro-Optics Products Corp., Flushing Meadows, N.Y., can be used. Thelight which has been both horizontally and vertically scanned isreflected via spherical mirrors 146 and 148 to the retina of the eye E.The light is scanned across an area of the retina whose extent isdetermined by the horizontal and vertical scanning extents of thescanning mirrors 138 and 144, which in turn are controlled by thecomputer 112.

Light reflected from the retina of the eye E travels back along thecommon optical path O, in which it is descanned by the scanning mirrors144 and 138, to a beam splitter 150 to be split between the lightdetection section 104 and the wavefront sensing section 106. The beamsplitter 150 can be implemented as a partially reflecting mirror,although an active beam splitter will be described in detail below.

The portion of the light diverted to the light detection section 104 isfocused by a lens 152 onto a confocal pinhole 154 which is in a planeconjugate to the retina. Light passing through the confocal pinhole 154is imaged by a photomultiplier tube 156 to produce signals which can beconverted into an image by the computer 112. The hardware used can be aGaAs photomultiplier tube from Hamamatsu, Japan, and a GenesisLC framegrabbing board from Matrox, Montreal, Quebec, Canada.

The portion of the light passed to the wavefront sensing section 106 iscollimated by lenses 158 and 160 and is passed to a Hartmann-Shackdetector 162. As known in the art, the Hartmann-Shack detector 162includes a lenslet array 164 which breaks up the light into an array ofspots and a CCD camera or other suitable imaging device 166 which imagesthe spots. The deviation of each spot from the position which it wouldoccupy in the absence of wavefront aberrations allows a determination ofthose aberrations in the computer 112. Techniques for determining theaberrations up to the tenth Zernike order are known in the art. Thecomputer 112 uses those aberrations to control the deformable mirror 128to compensate for those aberrations.

A drawback of using mirrors is that astigmatism and other aberrationsare introduced when they are off axis. To overcome that drawback, acylindrical correction can be placed in the spectacle plane of the eye,and optical design software such as ZEMAX, published by Focus Software,Tucson, Ariz., can be used to minimize the remaining high-order systemaberrations through optimal placement of the mirrors. Off-the-shelfspherical reflecting mirrors can be used.

The AOSLO 100 operates as shown in the flow chart of FIG. 2. In step202, the light delivery section 102 injects light into the commonoptical path O. In step 204, the scanning section 110 scans the retina.In an optional step 206, the retina can be axially scanned, in a mannerto be described below, to produce a three-dimensional image.

In step 208, the wavefront sensing section 106 senses the wavefrontaberrations. In step 210, the wavefront compensation section 108compensates for those aberrations. Steps 208 and 210 can be performediteratively.

In step 212, the light detection section 104 images the retina. In step214, the image of the retina is used for any desired purpose, includingdiagnosis of the retinal condition, surgery on the retina, applicationof therapeutic laser light to the retina, or eye movement tracking, aswill be explained in detail below.

As just noted, the steps of sensing and compensating the wavefrontaberrations can be performed iteratively. FIG. 3 shows the results ofsuch iterations for a 6.3 mm pupil in a living human eye. The x-axis isthe time in seconds over which the correction took place. Each pointrepresents the root mean square aberration after a single iteration. Themagnitude of aberrations, measured up to the tenth order in this case,is reduced sixfold for the 6.3 mm pupil.

A specific embodiment of the beam splitter 150 and its operation,namely, the timeshare embodiment, will be described. FIG. 4 shows agraph of the horizontal angular position of the horizontally scannedline on the retina as a function of time. As shown, the position is asinusoidal function of time, which has roughly linear sections. Duringthe linear section of each forward scan F, the scattered light isdetected by the light detection section 104 to image one line in a framein which the retina is imaged. During the linear section of each reversescan R, the scattered light is passed to the wavefront sensing section106 to measure the wavefront aberration.

The structure of the beam splitter 150 is shown in FIGS. 5A and 5B. Thebeam splitter 150 includes a disk 502 rotated by a motor 504. The disk502 has mirrored segments 506 alternating with non-mirrored segments508, so that the light is alternately reflected to the light detectionsection 104 and passed to the wavefront sensing section 106.

The reverse direction R of the scan can be used for wavefront sensing bysplitting the light between the wavefront sensor and the photomultipliertube with the segmented mirror that alternates between transmitting thelight to the wavefront sensor and reflecting the beam toward thephotomultiplier tube. The timing of the mirror is phase-locked to thehorizontal scan frequency. The light reaching the wavefront sensor canbe integrated for any desired period of time independently of the scanrate or the frame rate of a typical AOSLO. The aberrations of the eyechange dynamically and so the image quality will be better if the eye'saberrations are measured and compensated while the retina is imaged.

The deformable mirror can be used as an axial scanning element in axialsectioning. Axial sectioning requires an optical correction to changethe depth plane of the focused raster scan on the retina. The use of thedeformable mirror presents some unique advantages, which includereducing the number of moving parts in the system, and increasing itsspeed and precision. The thickness of the retina is about 300 microns. Afocal change of less than 1 diopter is sufficient to change the focalplane by this amount.

The present method can be implemented with the deformable mirrordescribed in the current design or it can be done with alternate,dynamic wavefront compensation techniques, such as micro-electricalmachined (MEMs) deformable mirrors, or membrane mirrors.

Wavefront sensing and correction can be done simultaneously with axialsectioning, in a technique called “non-null wavefront compensation.” Theoptical path for wavefront sensing is not confocal, so light is detectedfrom all scattered layers in the retina simultaneously. Therefore, whenthe aberrations of the eye are corrected, the defocus is also adjustedto put the focal plane into the mean location of all the scatteringlayers in the retina. If wavefront sensing and compensation were to bedone simultaneously with axial sectioning, the mirror would continuallytry to adjust its defocus to move the image plane back to the meanlocation of the scattering surfaces. Such a correction would defeatattempts to change the focal plane of the system and image differentlayers of the retina. This is overcome in the following way. Rather thanletting the AO system converge to a null state (i.e., zero aberrations),the AO system is programmed to converge to a finite defocused state. Byconverging to a defocused state, the AO system will adjust the focalplane, while still correcting all other aberrations to zero. Thistechnique will allow the operator to change the focal plane while stillhaving the benefit of simultaneous wavefront sensing and compensation.

The AOSLO described herein permits the direct imaging of features in theliving retina that have never been observed, features that includeretinal pigment epithelium cells, individual nerve fibers, cone and rodphotoreceptors, single capillaries in the retina and choroid and whiteblood cells. With the improvements in axial sectioning, it will bepossible to generate the first microscopic scale three-dimensionalimages of living human retina at high resolutions.

The AOSLO can be used for the diagnosis of retinal disorders likediabetic retinopathy, retinitis pigmentosa, age-related maculardegeneration, or glaucoma.

In still another use, high-resolution images of the retina will permithighly accurate measurements of eye movements needed for surgicalapplications or applications requiring eye tracking.

In yet another use, stimuli or treatment lasers are projected directlyonto the retina as part of the raster scan. Treatments includephotodynamic therapy, laser microphotocoagulation, and microperimetry ofthe retina.

Images have been collected from the eyes of five persons ranging in agefrom the 2^(nd) to 7^(th) decade. The RMS wavefront error after AOcompensation ranged from 0.05 to 0.15 μm over a 6.3 mm pupil. Thepatients used a dental impression mount fixed to an X-Y-Z translationstage to set and maintain eye alignment during the wavefront correctionand imaging. The retinal location of the wavefront correction andimaging was controlled by having each patient view a fixation target. Adrop of 1% tropicamide was instilled to dilate the pupil and to minimizeaccommodation fluctuations.

Experimental data will now be set forth. The correction of aberrationsprovided by the present invention permits retinal imaging of highquality, as will be seen.

FIGS. 6A and 6B show the same area of the retina of one patient takenwithout (FIG. 6A) and with (FIG. 6B) aberration correction. The RMSwavefront error was reduced from 0.55 to 0.15 μm. Another advantage wasthat correction of the aberrations caused more light to be focusedthrough the confocal pinhole, thus increasing the amount of light forimaging. The inset in each of FIGS. 6A and 6B shows a histogram of grayscales in the image.

FIGS. 7A-7C show axial sectioning of the retina, which is possiblebecause of the reduction in aberrations. The images are from a location4.5 degrees superior to the fovea. In FIG. 7A, the focal plane is at thesurface of the nerve fibers. FIG. 7B shows a slightly deeper opticalsection in which less nerve fiber is seen but the blood vessel is infocus. FIG. 7C shows an image in which the focal plane is at the levelof the photoreceptors, which are about 300 μm deeper than the image ofFIG. 7A.

FIG. 8 shows a sequence of video frames in which the passage of a whiteblood cell through the smallest retinal capillaries is directly observedin a living human eye. The scale bar at the bottom is 100 microns.

FIG. 9 shows images of cone photoreceptors resolved at retinal locationsfrom 0.5 to 4 degrees from the fovea. The long-dashed line shows datafrom Curcio et al, “Human photoreceptor topography,” J. Comp. Neurol.1990; 292:497-523, while the short-dashed line shows psychophysicalestimations of cone spacing from D. Williams, “Topography of the fovealcone mosaic in the living human eye,” Vision Res. 28, 433-454 (1988).

Preliminary estimates of the resolution of the present invention areabout 2.5 μm lateral and about 100 μm axial. By contrast, conventionalSLO's have a typical resolution of 5 μm lateral and 300 μm axial.

The AOSLO of the preferred embodiment operates at a frame rate of 30 Hz,which permits visualization of blood flow in the retinal capillaries.Also, the real-time imaging provides feedback on image quality and imagelocation. Further, axial sectioning can be implemented. Conventionalflood-illumination imaging, even with AO, cannot offer such advantages.

The following article concerning the present invention is herebyincorporated by reference in its entirety into the present disclosure:A. Roorda et al, “Adaptive optics scanning laser ophthalmoscopy,” OpticsExpress, Vol. 10, No. 9, May 6, 2002, pp. 405-412.

While a preferred embodiment of the present invention and variationsthereon have been disclosed above, those skilled in the art who havereviewed the present disclosure will readily appreciate that otherembodiments can be realized within the scope of the invention. Forexample, numerical values are illustrative rather than limiting. Also,variations on the configuration of the common optical path are possible,and variations on the hardware have been noted above. Further, while thepresent invention has been disclosed with regard to human subjects,veterinary applications are also possible. Therefore, the presentinvention should be construed as limited only by the appended claims.

1. A method of imaging an area of a retina of a living eye, the methodcomprising: (a) providing light from a light source; (b) injecting thelight from the light source into a common optical path; (c) scanning thelight from the light source on the area of the retina; (d) receivinglight reflected from the retina back into the common optical path; (e)from a first portion of the light reflected from the retina, detecting awavefront aberration of the eye; (f) disposing an adaptive opticalelement in the common optical path; (g) controlling the adaptive opticalelement to compensate for the wavefront aberration; and (h) from asecond portion of the light reflected from the retina, producing animage of the area of the retina.
 2. The method of claim 1, wherein step(d) comprises descanning the light reflected from the retina.
 3. Themethod of claim 1, wherein the adaptive optical element comprises adeformable mirror.
 4. The method of claim 1, wherein step (c) comprisesraster scanning a light spot on the retina.
 5. The method of claim 4,wherein the raster scanning is performed with at least one scanningmirror.
 6. The method of claim 5, wherein step (c) further comprisescontrolling a sweep angle of the at least one scanning mirror to controla size of an area on the retina which is scanned.
 7. The method of claim1, wherein step (e) is performed with a Hartmann-Shack detector.
 8. Themethod of claim 7, wherein: step (h) is performed with a photodetector;and the method further comprises providing a beam splitter in the commonoptical path to split the light reflected from the retina between theHartmann-Shack detector and the photodetector.
 9. The method of claim 8,wherein the beam splitter comprises a rotating mirror having mirroredsegments and transparent segments for time division of the lightreflected from the retina.
 10. The method of claim 9, wherein a periodof the time division equals a period of the scanning of step (c). 11.The method of claim 1, wherein steps (e) and (g) are performediteratively.
 12. The method of claim 1, wherein steps (e) and (h) areperformed concurrently.
 13. The method of claim 1, further comprising(i) controlling the adaptive optical element for axial sectioning. 14.The method of claim 13, wherein step (g) comprises correcting the focusto a non-null state.
 15. The method of claim 13, wherein step (h)comprises producing a three-dimensional image of the retina.
 16. Themethod of claim 1, further comprising using the image to diagnose adisorder of the retina.
 17. The method of claim 1, further comprisingusing the image to track movement of the eye.
 18. The method of claim 1,wherein step (c) comprises projecting a stimulus or treatment to theretina.
 19. The method of claim 1, wherein step (h) is performed aplurality of times to form a sequence of said images, and furthercomprising using the sequence of said images to measure a flow of bloodcells in at least one capillary of the retina.
 20. The method of claim1, wherein step (h) is performed with a confocal pinhole and aphotodetector.
 21. A system for imaging an area of a retina of a livingeye, the system comprising: a light delivery section, comprising a lightsource, for providing light from the light source and for injecting thelight from the light source into a common optical path; a scanningsection for scanning the light from the light source on the area of theretina such that light reflected from the retina is received back intothe common optical path; a wavefront sensing section, receiving a firstportion of the light reflected from the retina, for detecting awavefront aberration of the eye; a wavefront compensation section,comprising an adaptive optical element disposed in the common opticalpath, for compensating for the wavefront aberration; and a lightdetection section, receiving a second portion of the light reflectedfrom the retina, for producing an image of the area of the retina. 22.The system of claim 21, wherein the scanning section descans the lightreflected from the retina.
 23. The system of claim 21, wherein theadaptive optical element comprises a deformable mirror.
 24. The systemof claim 21, wherein the scanning section comprises a device for rasterscanning a light spot on the retina.
 25. The system of claim 24, whereinthe device for raster scanning comprises at least one scanning mirror.26. The system of claim 21, wherein the wavefront sensing sectioncomprises a Hartmann-Shack detector.
 27. The system of claim 26,wherein: the light detection section comprises a photodetector; and thesystem further comprises a beam splitter in the common optical path forsplitting the light reflected from the retina between the Hartmann-Shackdetector and the photodetector.
 28. The system of claim 27, wherein thebeam splitter comprises a rotating mirror having mirrored segments andtransparent segments for time division of the light reflected from theretina.
 29. The system of claim 21, wherein the light detection sectioncomprises a confocal pinhole.